Abstract

BackgroundAntibodies against citrullinated proteins (ACPA) have been recognised as the most specific serum marker for rheumatoid arthritis. However, serum autoantibodies such as anti-nuclear antibodies have also been detected in the sera of different lymphatic malignancies without accompanying rheumatologic disease. Therefore, we conducted a study to evaluate the prevalence of ACPA in diffuse large B-cell non-Hodgkin lymphoma (DLBCL).MethodsSera of 395 DLBCL patients and 258 age-matched healthy controls were investigated to evaluate the prevalence of ACPA and RF. ACPA-positive data were stratified into subgroups of RF positivity and established prognostic parameters for DLBCL, including overall survival. In addition, the ACPA serum concentrations levels were compared to an ACPA-positive RA cohort (n = 175). The statistics were performed with χ2 test and Mann- Whitney-U test; Kaplan-Meyer curves (log rank test) were used to analyse the overall survival. P-value <0.05 was statistically significant.ResultsACPA, but not RF, occurred significantly more frequently in the sera of DLBCL patients than in healthy controls (3.5% versus 0.8%, p = 0.030). However, the ACPA serum concentration levels were significantly lower than in RA patients (median 10.4 versus 124.1 U/ml, p = 0.0001). After subgroup stratification, ACPA positivity in DLBCL was significantly associated with male gender (4.4% versus 0%, p = 0.022; odds ratio 1.046, CI 1.014–1.079) and with RF-IgM seropositivity (1.77% versus 0%, p = 0.043), but not with prognostic parameters for DLBCL.ConclusionsDLBCL is associated with a significantly higher prevalence of ACPA, with an increased prevalence in male patients, and simultaneous RF-IgM positivity. However, ACPA is not prognostic for DLBCL. The prevalence of RF-IgM, -IgA, or -IgG did not differ from healthy controls.

Highlights

  • Patients with rheumatoid arthritis (RA) are at an increased risk of lymphoproliferative diseases such as myeloma and high-grade B-cell non-Hodgkin lymphoma (B-NHL) compared with the healthy population [1,2,3]

  • Serum biomarkers which are established in the diagnostic procedure and prognostic evaluation in RA such as rheumatoid factor (RF) or antinuclear antibodies (ANA) could be observed in the sera of patients suffering from different forms of lymphatic malignancy

  • The study population of lymphoma patients was well characterised with respect to all relevant clinical parameters, including previous medical history, stage of lymphoma disease, elevation of serum lactate dehydrogenase (LDH), patientsperformance status ECOG and overall survival using datasheets submitted to the biostatistics institution of Leipzig University

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Summary

Introduction

Patients with rheumatoid arthritis (RA) are at an increased risk of lymphoproliferative diseases such as myeloma and high-grade B-cell non-Hodgkin lymphoma (B-NHL) compared with the healthy population [1,2,3]. The antinuclear antibody (ANA) titre occurs in up to one third of sera derived from RA patients, predicting a severe course of disease and extra-articular manifestations [9]. Antibodies against citrullinated proteins (ACPA) have been recognised as the most specific serum marker for rheumatoid arthritis. Serum autoantibodies such as anti-nuclear antibodies have been detected in the sera of different lymphatic malignancies without accompanying rheumatologic disease. We conducted a study to evaluate the prevalence of ACPA in diffuse large B-cell non-Hodgkin lymphoma (DLBCL)

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